Atomic Description of an Enzyme Reaction Dominated by Proton Tunneling

Abstract

We present an atomic-level description of the reaction chemistry of an enzyme-catalyzed reaction dominated by proton tunneling. By solving structures of reaction intermediates at near-atomic resolution, we have identified the reaction pathway for tryptamine oxidation by aromatic amine dehydrogenase. Combining experiment and computer simulation, we show proton transfer occurs predominantly to oxygen O2 of Asp(128)beta in a reaction dominated by tunneling over approximately 0.6 angstroms. The role of long-range coupled motions in promoting tunneling is controversial. We show that, in this enzyme system, tunneling is promoted by a short-range motion modulating proton-acceptor distance and no long-range coupled motion is required.

Comparison of DFT and ab initio QM/MM methods for modelling reaction in chorismate synthase

“…The model was then solvated with a pre-equilibrated box of CHARMM-type TIP3P [23,24] water molecules and then truncated to a 25 Å sphere centered on the carbon atom C4 of EPSP (see Scheme 1). This procedure has been applied previously to model several other enzymes [19,25,26]. Combined QM/MM methods are a valuable tool in the growing area of computational enzymology [2].…”

Measurement of Proton Tunneling in Short Hydrogen Bonds in Single Crystals of 3,5 Pyridinedicarboxylic Acid Using Nuclear Magnetic Resonance Spectroscopy

“…Proton tunneling in longer HBs has also been shown to enhance the enzymatic rate through its nonclassical dependence on the proton (H=D=T) mass-the kinetic isotope effect [13,14]. In addition, as demonstrated for simpler molecular systems [15][16][17], the coupling between large amplitude PT with small amplitude vibrations has been observed in enzymes by isotopic substitution of the molecular skeleton in the vicinity of the active HBs [18].…”

“…Experimental observations and numerical modeling show that the 1 H spin-lattice relaxation rate is closely approximated by the diagonal element of the relaxation matrix. Furthermore, the modulation of the heteronuclear 14 …”

Wide-dynamic-range kinetic investigations of deep proton tunnelling in proteins

“…Thus, the experiments presented here, which are the first temperature dependent measurements of tunneling in a biological proton wire and cover a much larger temperature range than previous studies 2,3,5,9 , can help us to better understand this important process. Because the deep tunneling rate is so exquisitely sensitive to tunnel-distance variations, it has the potential to play an important role in controlling transport along protein wires or in enzymatic reactions 5,19,20 .…”

“…Proton transport (PT) in biological systems has been the subject of many studies, both experimental [1][2][3][4][5][6] and theoretical [7][8][9][10][11][12] . A better understanding of this phenomenon is sought because it underpins so many fundamental life processes [13][14][15][16][17][18] .…”